The use of human blood and blood plasma is so widespread that much work has been directed to blood handling systems, including specifically plasmapheresis systems for extraction of plasma from whole blood. While centrifugation was primarily used in the past in preference to membrane filtration techniques, more recent breakthroughs in membrane filtration technology have occurred that are effecting widespread changes. New plasmapheresis systems are based upon the usage of a vortex enhanced fractionation approach which uses a rotating spinner within a shell, with the surface of the spinner or shell being covered with a filtration membrane. Relative velocities and blood flow conditions are established such that constantly sweeping vortices appear along the length of the spinner to continually present fresh plasma to the surface of the membrane while maintaining high shear conditions. This action enables plasma to be filtered through the membrane without depositing cellular or other matter on the membrane surface so as to increasingly clog the pores of the membrane.
A particular example of this type of system is described in a patent application by Donald W. Schoendorfer entitled "Method And Apparatus For Separation Of Matter From Suspension", Ser. No. 591,925, filed Mar. 21, 1984. With rotating spinner devices of this type, substantially higher plasma flow rates per unit of membrane surface area are obtained than with prior membrane systems, enabling the manufacture of low cost disposable filtration units that can extract two or three units of plasma with minimal donor discomfort and time commitment.
In plasmapheresis systems it is necessary to use an anticoagulant in an amount sufficient to minimize blood clotting but below the level at which adverse physiological effects occur. Automated plasmapheresis systems have typically employed from approximately 10% to approximately 4% of known citrate solutions for restricting clotting tendencies.
In operating plasmapheresis systems using a rotating spinner and vortex action, trauma to the blood is low and it is feasible to utilize anticoagulant at the lower end of the permissible range for most donors. Using a membrane of approximately 60 cm.sup.3 in area, plasma "take" rates of 35 ml/min are expected, so that a donor time of approximately 30 minutes is established for about 500 ml of blood. This time interval includes, in a single needle system, periodic dwell periods during which the plasmapheresis system returns packed cells to the donor. During these dwell periods no whole blood flows through the plasmapheresis device and the spinner might not be rotated, so that the blood then in the device is in a static or quasi-static condition. During these dwell periods the blood sometimes reacts with the filter. When this reaction occurs the flow rate through the filter is thereafter significantly reduced. Some flow reduction may also occur during the active periods.
Clinical studies and detailed analysis have shown that this flow reduction occurs with a minor percentage of the donor population, approximately 10%. The difference between this subpopulation of donors and the majority of donors is not fully understood, and the problems appears at this time to pose complex problems that will not be easily resolved. It is not currently known, for example, whether the substandard flow condition arises from a constant donor characteristic or is related to diet, physiological changes or other time variable factors. Thus there is no way to identify specific members of the subpopulation until they have been coupled into the system. It is nonetheless desirable to have an essentially standardized system and clinical procedure for the extraction of plasma from the donor population. It is also a fundamental objective to provide a procedure which gives a substantially constant rate of take of plasma or other constituent.
Extensive investigations as to the functional operation of the filtration process did not reveal the reason for the existence of a special subpopulation. Furthermore, review of the literature as to effects of various levels of anticoagulant were not instructive. Although there have been many investigations of biochemical aspects of the coagulation mechanism, these do not clarify the increase in deposition and consequent lowering of filtration rate in a cyclically operated filtration system. Despite the fact that the effects of fluid characteristics such as pH and ion concentration on blood cells have been extensively studied in a non-shear, storage type environment, the effects in a high shear environment have not been well defined.